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Review
. 2020 Nov 24:8:606039.
doi: 10.3389/fcell.2020.606039. eCollection 2020.

Organotypic Modeling of the Tumor Landscape

Affiliations
Review

Organotypic Modeling of the Tumor Landscape

Maria M Haykal et al. Front Cell Dev Biol. .

Abstract

Cancer is a complex disease and it is now clear that not only epithelial tumor cells play a role in carcinogenesis. The tumor microenvironment is composed of non-stromal cells, including endothelial cells, adipocytes, immune and nerve cells, and a stromal compartment composed of extracellular matrix, cancer-associated fibroblasts and mesenchymal cells. Tumorigenesis is a dynamic process with constant interactions occurring between the tumor cells and their surroundings. Even though all connections have not yet been discovered, it is now known that crosstalk between actors of the microenvironment drives cancer progression. Taking into account this complexity, it is important to develop relevant models to study carcinogenesis. Conventional 2D culture models fail to represent the entire tumor microenvironment properly and the use of animal models should be decreased with respect to the 3Rs rule. To this aim, in vitro organotypic models have been significantly developed these past few years. These models have different levels of complexity and allow the study of tumor cells alone or in interaction with the microenvironment actors during the multiple stages of carcinogenesis. This review depicts recent insights into organotypic modeling of the tumor and its microenvironment all throughout cancer progression. It offers an overview of the crosstalk between epithelial cancer cells and their microenvironment during the different phases of carcinogenesis, from the early cell autonomous events to the late metastatic stages. The advantages of 3D over classical 2D or in vivo models are presented as well as the most promising organotypic models. A particular focus is made on organotypic models used for studying cancer progression, from the less complex spheroids to the more sophisticated body-on-a-chip. Last but not least, we address the potential benefits of these models in personalized medicine which is undoubtedly a domain paving the path to new hopes in terms of cancer care and cure.

Keywords: 3D model; cancer; metastasis; therapies; tumor dissemination; tumor microenvironment.

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Figures

FIGURE 1
FIGURE 1
The tumor microenvironment influences the different stages of cancer progression. The primary tumor is infiltrated by different immune subsets and surrounded by a remodeled matrix. Angiogenesis ensures tumor growth by supplying nutrients and also provides a route for metastasis. Intravasation of tumor cells into blood vessels allows their shuttling to a novel site. The secondary site is primed by exosomes secreted by tumor cells and the different actors of the TME to allow the successful seeding of incoming tumor cells. TAM, Tumor-associated macrophage; ECM, Extracellular matrix; CAA, Cancer-associated adipocytes; MDSC, Myeloid-derived suppressor cells; CAF, Cancer-associated fibroblast; TME, Tumor microenvironment.
FIGURE 2
FIGURE 2
Organotypic in vitro models of cancer progression with increasing biological complexity from the simple multicellular spheroid model to the more complex microfluidic approaches. TME, Tumor microenvironment; MCS, Multicellular spheroid; HTS, High-throughput screening; ECM, Extracellular matrix.

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